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R T Falk

Publications and source records attributed to R T Falk.

At least 37 records · Page 2Linked to original sources
PubMed1994

Reproducibility of laboratory assays for steroid hormones and sex hormone-binding globulin.

The relationship of serum hormones to cancer risk has recently been pursued in epidemiological studies, but few have reported on the reproducibility of laboratory findings. Prior to conducting a study of endogenous hormones and endometrial cancer, we evaluated the reproducibility of measurements for several hormones (estrone, estradiol, free estradiol, albumin-bound estradiol, and androstenedione) and sex hormone-binding globulin. We obtained a single unit of blood from each of six women and prepared aliquots of serum for repeated testing. Three laboratories analyzed multiple samples on consecutive working days from which estimates of intraassay and interassay measurement variability were obtained. For estrone and estradiol, a log transformation of the data produced distributions which were nearly normal and permitted the use of parametric statistical tests. In general, we found measurements for most hormones varied considerably between assays. Moreover, differences were observed in the absolute values of sex hormone-binding globulin and of the hormones, particularly for estrone and estradiol, from one laboratory to the next. Our findings suggest that variability of current laboratory procedures may hamper efforts to study the association between disease and endogenous hormones in epidemiological studies. In addition, validation of hormone assays is essential in order to assure standardized results and enable comparisons of data across studies.

Androstenedione↗
PubMed1994

Lung tumor resection does not affect debrisoquine metabolism.

Some authors have reported an association of extensive metabolism of debrisoquine with increased lung cancer risk, although others have found no association. Debrisoquine metabolism is controlled by a cytochrome P-450 isozyme encoded at the CYP2D6 locus, which is inducible by antipyrine and rifampicin. Because lung tumors may produce a variety of humoral substances, we wanted to determine whether the tumor induced debrisoquine metabolism. As part of a case-control study of lung cancer, debrisoquine metabolism was measured in patients with histologically confirmed non-small cell lung cancer before and after surgical resection with curative intent. One hundred four incident patients with curative intent. One hundred four incident patients with pathological stage I, II, or IIIA non-small cell lung cancer took debrisoquine (10 mg) orally at 10 p.m. and collected the subsequent 8-h urine both before and after surgery. We compared the values of the metabolic ratio, which is the percentage of the dose excreted as debrisoquine to the percentage of the dose excreted as the principal metabolite. The pre- and postoperative metabolic ratios were highly correlated (Pearson correlation coefficient = 0.96), and did not differ in value significantly (P = 0.88). Using traditional cutpoints (metabolic ratio, 1.0 and 12.6) to categorize the three metabolic phenotypes, the preoperative and postoperative phenotypes were well correlated (kappa = 0.78). These results show that the ability to metabolize debrisoquine is not induced by the presence of a primary lung tumor.

Carcinoma, Non-Small-Cell Lung↗
PubMed1993

Role of HTLV-I in development of non-Hodgkin lymphoma in Jamaica and Trinidad and Tobago. The HTLV Lymphoma Study Group.

Human T-cell lymphotropic virus type I (HTLV-I) has been implicated in the aetiology of adult T-cell leukaemia/lymphoma in Japan and elsewhere, particularly the Caribbean. We have carried out parallel case-control studies in Jamaica and in Trinidad and Tobago to quantify the role of HTLV-I in the development of non-Hodgkin lymphoma (NHL). 135 cases of NHL were enrolled in Jamaica and 104 in Trinidad and Tobago. Controls were selected from patients treated in the same wards or clinics at the same time as the cases. Overall, patients with NHL were 10 times more likely than were controls to be seropositive for HTLV-I (Jamaica odds ratio 10.3 [95% CI 6.0-18.0], Trinidad and Tobago 14.4 [7.6-27.2]). In both countries the association between NHL and HTLV-I was greatest for T-cell lymphomas (18.3 [9.5-35.6] and 63.3 [25-167]). Among T-cell lymphomas especially, there was no significant difference between men and women in the association between NHL and HTLV-I, but there was a significant inverse relation between age and likelihood of HTLV-I seropositivity. B-cell lymphomas were predominant in the older age groups and were not associated with HTLV-I seropositivity. These findings are consistent with the hypothesis that early life exposure to HTLV-I is important for risk of subsequent ATL. Prevention of vertical transmission of HTLV-I could reduce by 70-80% cases of NHL in people under 60 years in this region.

Adult↗
PubMed1993

Clustering of high density lipoprotein cholesterol levels in premenopausal and postmenopausal female twins.

Previous family and twin studies indicate that genetic variation makes an important contribution to individual variation in high density lipoprotein cholesterol (HDL) levels, even after adjustment for covariates (such as obesity and alcohol consumption) that also cluster in families. However, most studies assume that genetic mechanisms affecting variation in HDL level are the same in all subgroups of the population (e.g., men versus women, by age). Using data from the Kaiser-Permanente Women Twins Study, we found different patterns of clustering for monozygotic (MZ) and dizygotic (DZ) twins depending on menopausal status. Premenopausal MZ twins were more similar than postmenopausal MZ twins (r(i) = 0.79 and r(i) = 0.61, respectively, after adjustment for age, alcohol consumption, smoking status, degree of obesity, and leisure-time exercise); premenopausal and postmenopausal DZ twins were alike to the same extent (r(i) = 0.31 and r(i) = 0.32, respectively, adjusted as above). These data suggest that either postmenopausal MZ twins have a greater degree of shared environment than postmenopausal DZ twins (e.g., postmenopausal female hormone use) or that genetic mechanisms that affect individual variation in HDL level differ in pre- and postmenopausal women. Data were not available on postmenopausal female hormone use. If genetic mechanisms that influence variation in HDL levels differ between pre- and postmenopausal women, genetic epidemiologic methods that assume that genetic and environmental sources of variation are the same for all groups of individuals may lead to false conclusions.

Adult↗
PubMed1993

Race and sex differences in associations of vegetables, fruits, and carotenoids with lung cancer risk in New Jersey (United States).

We used data from a case-control study conducted in New Jersey between 1980 and 1983 to evaluate race and sex differences in associations of vegetable, fruit, and carotenoid consumption with lung cancer. Cases included 736 White males, 860 White females, 269 Black males, and 86 Black females with incident, histologically confirmed, primary cancer of the trachea, bronchus, or lung. Controls were identified through drivers' license and Health Care Financing Administration files and included 548 White males, 473 White females, 170 Black males, and 47 Black females. Usual intakes of vegetables (predominantly yellow/green) and fruit (predominantly yellow/orange) as well as other food sources of carotenoids were ascertained by a food frequency questionnaire. White females showed significant inverse associations of lung cancer with vegetables, fruit, and carotenoids. White males showed nonsignificant inverse associations with vegetables and carotenoids, and Black females just with vegetables. No inverse associations were found for Black males. Vegetable consumption was associated with risk of all histologic types of lung cancer, but the pattern of increasing risk with decreasing intake was limited to smokers. We infer that consumption of yellow/green vegetables and carotenoids may confer protection from lung cancer to White male and White female smokers. Further studies are needed to clarify the effect in Blacks.

Black or African American↗
PubMed1991

Lung cancer risk associated with cancer in relatives.

Family history data from an incident case-control study of lung cancer conducted in the Texas Gulf Coast region between 1976 and 1980 were analyzed to evaluate the contribution of cancer in first-degree relatives to lung cancer risk. Odds ratios (OR) increased slightly as the number of relatives with any cancer increased (reaching 1.5 with 4 or more relatives with cancer). Risks were higher for tobacco-related cancers (OR = 1.5 for 2 or more relatives with these tumors) and greatest for first-degree relatives with lung cancer (OR = 2.8 for lung cancer in 2 or more relatives). For cases of squamous cell carcinoma and adenocarcinoma of the lung, risks with 3 or more relatives with any cancer were increased 2-fold (OR = 1.8 and 1.9 respectively), and a significantly elevated risk was found for having a first-degree relative with lung cancer for each histologic type (ORs from 1.7-2.1). Having a spouse with lung cancer increased lung cancer risk (OR = 2.5), and cases with lung cancer reported in a first-degree relative were diagnosed at an earlier age, as were case siblings with lung cancer.

Adenocarcinoma↗
PubMed1990

Occupation and pancreatic cancer risk in Louisiana.

To study the relation of occupational exposures and pancreatic cancer, we evaluated data from males (198 cases and 209 controls) participating in a hospital-based case-control study conducted in a high-risk area of Louisiana between 1979 and 1983. The questionnaire obtained information on lifetime occupational history, as well as dietary, smoking, and drinking habits and demographic characteristics. After adjustment for smoking and dietary patterns, white collar occupations showed consistent elevations in risk, whereas associations for other occupations were in general unremarkable. Although not significantly elevated, risks for truck drivers (OR = 1.7) and those with long-term employment in machine repair or as mechanics were suggestive (OR = 2.5). No association was found for jobs in oil refining or oil and gas extraction (ORs were 0.5 and 0.4, respectively), although risks were slightly elevated for long-term workers in the chemical processing industry (OR = 1.2). While these associations deserve further study, our findings are consistent with results of other studies which do not suggest that occupational exposures are important determinants of pancreatic cancer.

Adenocarcinoma↗
PubMed1990

A problem in identifying risk factors for disease using surrogate exposure variables that are under genetic control.

The use of a surrogate exposure variable to represent a complex of genetic and/or nongenetic factors is commonplace in epidemiologic studies. The authors present an hypothetical example in which a surrogate exposure results from underlying unknown genetic and nongenetic factors, yet only the genetic component predisposes to disease. The results demonstrate how risk may be incorrectly attributed to the nongenetic component of exposure and suggest a possible explanation for the identification of a risk factor in one case-control study in one population, but not in another study of the same disease conducted in a different population.

Case-Control Studies↗
PubMed1989

Effect of smoking and alcohol consumption on laryngeal cancer risk in coastal Texas.

Data from case-control studies of respiratory cancer conducted in the Texas Gulf Coast region between 1975 and 1980 were used to examine the effects of smoking and alcohol on laryngeal cancer risk. Analyses were limited to living white males, aged 30-79, which included 151 histologically confirmed incident laryngeal cancer cases and 235 population-based controls. A dose-dependent effect for cigarette smoking was observed, with odds ratios ranging from 4.4 for ever smoking up to one-half pack daily, to 10.4 for smoking more than two packs per day. Risks were strongest for current smokers and declined markedly following smoking cessation. Higher risks were associated with smoking nonfiltered than filtered cigarettes. No significantly elevated risks were associated with the use of other tobacco products. Odds ratios for alcohol beverages did not increase linearly with increasing use; instead risks were twofold for consumption of four or more drinks weekly. Patterns of risk associated with beer and hard liquor were not consistent and few participants drank wine. Although the data were sparse, a dose-response effect for alcohol intake was suggested for tumors of the supraglottis (n = 23), while for nonsupraglottic cases, alcohol risks were elevated but did not increase beyond those observed for four drinks per week. Predicted risks for the combined effects of cigarette and alcohol use were intermediate between an additive and multiplicative form of interaction.

Adult↗
PubMed1988

Dietary vitamins A and C and lung cancer risk in Louisiana.

The authors describe the results of a hospital-based incident case-control study of lung cancer conducted in a high-risk region of southern Louisiana from January 1979 through April 1982. Dietary intake of carotene, retinol, and vitamin C was estimated from food frequency questionnaires administered to 1253 cases and 1274 controls. An inverse association was found between level of carotene intake and lung cancer risk, and this protective effect was specific for squamous and small cell carcinoma (odds ratio [OR] = 0.84, 95% confidence interval: 0.64-1.09, high intake). A stronger protective effect for these tumors was associated with dietary vitamin C intake (OR = 0.65, 0.50-0.87, high intake). A significant inverse gradient in risk with retinol intake was limited to adenocarcinoma (OR = 0.64, 0.44-0.94, high intake) and more pronounced among blacks.

Adult↗
PubMed1988

Life-style risk factors for pancreatic cancer in Louisiana: a case-control study.

A hospital-based, incident case-control study of pancreatic cancer was conducted between 1979 and 1983 in parallel with similarly designed studies of lung and stomach cancers in high-risk areas of Louisiana. To evaluate life-style practices, including diet, the authors pooled controls from the three studies, and then excluded subjects with diet-altering chronic diseases. When the 363 cases were compared with the 1,234 identified controls, significantly elevated risks were found among persons with Cajun ancestry, especially in rural areas. Among current smokers, a significant twofold risk was associated with moderate (16-25 cigarettes per day) and heavy (greater than or equal to 26 cigarettes per day) consumption, while ex-smokers showed no consistent pattern of risk. After adjustment for potential confounding by smoking, diet, and demographic factors, the risk of pancreatic cancer was unrelated to use of alcoholic beverages or coffee. Pork products and rice were conspicuous as dietary risk factors, each showing a positive dose-response effect, whereas fruit consumption exerted a protective influence.

Aged↗
PubMed1988

Clinical features and history of the destructive lung disease associated with alpha-1-antitrypsin deficiency of adults with pulmonary symptoms.

Alpha-1-antitrypsin (alpha 1AT) deficiency is a hereditary disorder characterized in adults by a high risk for the development of severe destructive lung disease at an early age. The present study was designed to draw conclusions concerning the characteristics of a referral population of 124 patients with alpha 1AT deficiency and symptomatic emphysema. Typically, the alpha 1AT level was 30 mg/dl, and the alpha 1AT phenotype was almost always PiZZ. The individuals in this population were most often male, caucasian, and ex-smokers, and they had become dyspneic between 25 and 40 yr of age. Most routine blood tests were normal. The chest radiographs and ventilation-perfusion studies typically showed abnormalities with a lower zone distribution, and about one third of the study population had evidence suggestive of pulmonary hypertension. Lung function tests were typical for emphysema; the FEV1 and DLCO were the parameters most dramatically reduced, and the annual rate of decline of those parameters was greater than that of the general population. The cumulative probability of survival of this population indicated a significantly shortened lifespan with a mean survival of 16% at 60 yr of age compared with 85% for normal persons.

Adolescent↗
PubMed1984

Membrane current following activity in canine cardiac Purkinje fibers.

Membrane current following prolonged periods of rapid stimulation was examined in short (less than 1.5 mm) canine cardiac Purkinje fibers of radius less than 0.15 mm. The Purkinje fibers were repetitively stimulated by delivering trains of depolarizing voltage clamp pulses at rapid frequencies. The slowly decaying outward current following repetitive stimulation ("post-drive" current) is eliminated by the addition of 10(-5) M dihydro-ouabain. The post-drive current is attributed to enhanced Na/K exchange caused by Na loading during the overdrive. Depolarizing voltage clamp pulses initiated from negative (-80 mV) or depolarized (-50 mV) holding potentials can give rise to post-drive current because of activation of tetrodotoxin-sensitive or D600-sensitive channels. The magnitude of the post-drive current depends on the frequency of voltage clamp pulses, the duration of each pulse, and the duration of the repetitive stimulation. The time constant of decay of the post-drive current depends on extracellular [K] in accordance with Michaelis-Menten kinetics. The Km is 1.2 mM bulk [K], [K]B. The mean time constant in 4 mM [K]B is 83 s. Epinephrine (10(-5) M) decreases the time constant by 20%. The time constant is increased by lowering [Ca]o between 4 and 1 mM. Lowering [Ca]o further, to 0.1 mM, eliminates post-drive current following repetitive stimulation initiated from depolarized potentials. The latter result suggests that slow inward Ca2+ current may increase [Na]i via Na/Ca exchange.

Animals↗
PubMed1983

Voltage-clamp studies on the canine Purkinje strand.

Purkinje strands were excised from the left and right ventricles of adult mongrel dogs and cut to lengths of less than 2.0 mm in order to apply the two-microelectrodes voltage-clamp technique. A sizeable fraction of these preparations fully recover following dissection, with resting potentials more negative than--80 mV and upstroke velocities faster than 290 V s-1. Analysis of the voltage response to small current pulses shows that the short Purkinje strands can be treated as simple finite one-dimensional cables with ends of infinite resistance. The average length constant is 2.5 mm. In keeping with the relatively long length constant, insertion of a third microelectrode along the strand demonstrates a high degree of longitudinal homogeneity of the voltage clamp. Analysis of the capacity transient gives an estimate of the total capacity, normalized to cylindrical surface area, of 11.5 muF cm-2. The final decay of the capacity transient is a single exponential with an average time constant of 1 ms. A second slower component to the final decay of the capacity transient is absent in solutions of normal conductivity as well as in solutions of reduced (13%) conductivity. This suggests that the extracellular series resistance may be relatively small. The magnitude of the K+ depletion current was estimated by measuring the ratio of depletion current to instantaneous current. This ratio averaged 10%. These two results are consistent with the morphometric data described in the accompanying paper, which show that the canine preparation has wider extracellular clefts than the ungulate preparation. The existence of the full complement of inward and outward currents, including the pacemaker current, is demonstrated. The presence of wide clefts does not affect the potential at which the pacemaker current reverses (about--107 mV in 4 mM [K+] Tyrode solution), since the pacemaker current reverses at approximately the same potential in the canine Purkinje preparation as it does in the ungulate.

Action Potentials↗
PubMed1983

Actions of barium and rubidium on membrane currents in canine Purkinje fibres.

The actions of Ba2+ and Rb+, two blockers of background K+ conductance, were investigated. Recent studies performed on ungulate Purkinje fibres have suggested that the pace-maker current is an inward current activated by hyperpolarization. This hypothesis is based on the assumption that Ba2+ reduces the inwardly rectifying background K+ conductance without affecting the pace-maker current. Addition of 5 mM-BaCl2 to the bathing Tyrode solution decreases background K+ permeability and eliminates the reversal of the pace-maker current. The reversal reappears on return to Ba2+-free Tyrode solution. 5 mM-BaCl2 also reduces the time-dependent current at pace-maker potentials positive to about -95 mV in 4 mM-K+ Tyrode solution. The pace-maker current in Ba2+ Tyrode solution usually does not have an exponential time course, and often decays non-monotonically. It can take more than two minutes to reach a steady state. The fast initial component of membrane current, which is observed on hyperpolarizing in the pace-maker potential range in Purkinje fibres and which has been called the 'depletion current', is still present in Ba2+ Tyrode solution, but is reduced or eliminated if 10 mM-CsCl is added to the Ba2+ Tyrode solution. The addition of Cs+ is accompanied by an outward shift in membrane current in Ba2+ Tyrode solution. Ba2+ reduces the background K+ permeability in a dose-dependent manner. Addition of between 0.5 and 1 mM-BaCl2 achieves a maximum effect. Raising the amount of BaCl2 above this level reduces the time-dependent current even when no further effect on background permeability is observed. Rb+ substitution for K+ reduces the magnitude of the pace-maker current at potentials positive to -100 mV, eliminates the reversal of the pace-maker current, shifts the activation range to more negative potentials, and decreases the voltage dependence of pace-maker current kinetics. Rb+ addition to Tyrode solution has little effect on pace-maker current magnitude or time course positive to -90 mV, but does shift the reversal to more negative potentials. The available evidence suggests that the pace-maker current in Ba2+ Tyrode solution is an inward current activated by hyperpolarization. However, Ba2+ blocks an unknown fraction of the pace-maker current in a dose-dependent, and possibly voltage-dependent manner. Also, the presence of a slow component of pace-maker decay suggests that the standard Hodgkin-Huxley formalism for the analysis of pace-maker currents is inappropriate.

Action Potentials↗
PubMedDate not supplied

Epidemiology of bronchioloalveolar carcinoma.

Descriptive features of bronchioloalveolar carcinoma (BAC) are presented using Surveillance, Epidemiology and End Results Program population-based incidence data from 1973 through 1987, along with risk factors from histologically confirmed cases of BAC identified in a hospital-based case-control study conducted in Louisiana between 1979 and 1982. Compared to the rising incidence of lung cancer overall, BAC rates have remained relatively constant, accounting for less than 3% of all lung cancer. BAC incidence rates were higher in males, yet it explained proportionately more of the total lung cancer incidence in females. In the case-control study, 21 of the 33 cases originally ascertained from hospital pathology records were histologically confirmed as BAC. Most cases smoked cigarettes, with a 4-fold risk for ever smoking. Risks tended to increase with smoking intensity (reaching 10-fold for more than 1.5 packs/day) and duration (reaching 5-fold for more than 45 years of smoking). Following 10 or more years of employment, there was a 4-fold risk associated with motor freight occupations, along with nonsignificant excesses among construction workers, petroleum manufacturers, and sugar cane farmers. Cases were more likely than controls to have had emphysema or to have had a close family member with lung cancer. Although based on small numbers, this study suggests that BAC shares many of the epidemiological characteristics of lung adenocarcinoma.

Adenocarcinoma, Bronchiolo-Alveolar↗
PubMedDate not supplied

Debrisoquine metabolism and lung cancer risk.

Previous reports of the association between the debrisoquine metabolic polymorphism and lung cancer risk have been conflicting. We examined the hypothesis that the genetically determined ability to metabolize debrisoquine identifies individuals at increased risk for lung cancer in a study designed to address some of the methodological criticisms of previous studies. A case-control study of 335 incident Caucasian lung cancer patients and 373 controls matched for age, race, sex, and hospital, was conducted at the National Naval Medical Center (Bethesda, MD) and at the Laval Hospital (Sainte-Foy, Quebec, Canada). Debrisoquine metabolic phenotype was determined by debrisoquine administration and analysis of debrisoquine and 4-hydroxydebrisoquine in the subsequent 8-h urine collected. Stratified and logistic regression analyses were used to evaluate the association between extensive or intermediate debrisoquine metabolism and lung cancer risk. We found no increased risk among extensive or intermediate metabolizers (odds ratio, 0.6; 95% confidence interval, 0.3-1.2). The lack of an association was not confounded by control diagnoses, medications used within 1 month of debrisoquine administration, smoking, stage, or histology of lung cancer. No relationship was found among either heavy smokers or light and nonsmokers. Our results do not support the role of debrisoquine metabolism as a marker for lung cancer risk. While the concept that polymorphisms of metabolism may account for differential susceptibility to lung cancer is sound, debrisoquine metabolic phenotype was not associated with lung cancer risk in these data.

Aged↗